Homeostasis del peso corporal: Factores genéticos

Se habla del componente hereditario de la regulación del peso corporal. Los datos de los que se dispone en la actualidad sugieren que entre el 40-70% de la variación en los fenotipos de ganancia de peso/obesidad está mediada genéticamente. El número de genes, marcadores y regiones cromosómicas que han sido relacionadas con fenotipos de obesidad en humanos continúa aumentando y en la actualidad ya se han descrito más de 600

Influencia del ambiente y la alimentación en la programación epigenética de la obesidad

El término epigenética hace referencia a los patrones hereditarios de la expresión de genes que se mantienen estables y que su- ceden sin que haya cambios en la secuencia de ADN. Los principales cambios en el patrón epigenético son: la metilación del ADN y la diferente organización de las histonas. Hay evidencias de que la metilación del genoma varía según los tejidos, los individuos o las condiciones de enfermedad, y se ha visto que la desorganización de la impronta genómica está relacionada con diferentes enfermeda- des en adultos, entre las que se encuentran la obesidad y/o el síndrome metabólico. El establecimiento de las marcas epigené- ticas durante el desarrollo puede estar in- fluenciado por factores ambientales como la dieta, principalmente por medio de nutrientes donantes de grupos metilo. Las alteraciones epigenéticas pueden ser debidas a la dieta parental (anterior al desarrollo intrauterino), al ambiente intrauterino y a la alimentación materna durante el embarazo, así como a las características de la alimentación peri y posnatal. Estas alteraciones epigenéticas INTRODUCCIÓN La programación de la obesidad puede darse por medio de al- teraciones permanentes de una o más vías relevantes durante el desarrollo embrionario y perinatal. Así, un tipo de alteraciones que afectan al desarrollo de obesidad y de síndrome metabólico en la edad adulta lo conforman los cambios en el patrón epige- nético. Dado que la obesidad es fundamentalmente un desor- den del balance energético, en el cual la energía ingerida excede pueden conservarse en el tiempo a través de sucesivas generaciones por su transmisión a la descendencia. A pesar de lo que ya se sabe, se necesitan nuevos trabajos que estudien los efectos de la alimentación en el estado epigenético del genoma y sus repercusiones fenotípicas a largo plazo para conocer mejor las posibles causas de la obesidad así como para diseñar nuevas estrategias para su prevenció

Genetics of obesity: gene x nutrient interactions

Obesity results from a long-term positive energy balance, in which gene-related differences may account for some of the disparities found in weight gain among populations. However, the rising prevalence of obesity in developed and developing societies must reflect lifestyle changes. Despite that the genetic background remains stable over many generations, obesity may be derived from a failure on the homeostasis systems, as a consequence of a dysfunction at the genetic level, which may be affected by changing environmental exposure (dietary habits, sedentarism, etc). In practice, obesity risk at least depends on two important factors, which mutually interact: 1) genetic variants and gene expression changes in candidate genes and 2) exposure to environmental risk factors. Disagreements among studies involving gene-nutrient interactions may reflect the difficulty of accurate measurement of specific types of dietary macro and micronutrients intake as well of phenotype assessment rather than a discrepancy in biological relevance. Identification of individuals who are genetically more likely to respond to particular dietary changes may be important for successful intervention in obesity treatment, since gene screening will allow health professionals to tailor-design weight management and dietary guidance in individuals with a genetic predisposition to become obese

Obesity and immunocompetence

The increasing worldwide prevalence of obesity is a major health problem since excessive body weight constitutes a risk factor in a number of chronic diseases. It has been reported that obese individuals are more susceptible to infection than lean subjects; however, the underlying factors are not fully understood. Limited and often controversial information exists comparing immunocompetence in obese and nonobese subjects as well as the cellular and molecular mechanisms involved, although much evidence supports a link between adipose tissue metabolism and immunocompetent cell functions. The complexity and heterogeneity of nutritional status and immune system interactions require an integral study of the immunocompetent cells, their subsets and products, as well as specific and non-specific inducer/regulatory systems in situations of human obesity. Additional research is needed to determine the clinical implications of these alterations on immunity and whether various interventions such as weight loss, exercise or nutrient supplementation could help to ameliorate them

Changes in UCP mRNA expression levels in brown adipose tissue and skeletal muscle after feeding a high-energy diet and relationships with leptin, glucose and PPARgamma

Brown adipose tissue and skeletal muscle are known to be important sites for nonshivering thermogenesis. In this context, it is accepted that uncoupling proteins (UCPs) are involved in such process, but little is known about the physiological regulation of these proteins as affected by the intake of a high-energy (cafeteria) diet inducing fat deposition. In this study, the UCP messenger RNA (mRNA) expression in interscapular brown adipose tissue (iBAT) and skeletal muscle was assessed to evaluate the influence of a dietary manipulation on energy homeostasis regulation. We report a statistically significant increase in mRNA levels of iBAT UCP1 and UCP3 and a statistical marginal rise in skeletal muscle UCP3 mRNA expression after feeding a high-energy diet, whereas no changes in UCP2 expression were found in either tissue. Furthermore, significant positive associations between iBAT UCP1 and UCP3 mRNA levels with serum leptin were found. Although the expression of the b3 adrenoceptor (b3AR) was about 50% in the lean controls compared with the obese group in iBAT, no statistically significant changes were observed concerning peroxisome proliferator-activated receptor g2 (PPARg2) mRNA levels in muscle or iBAT. We conclude that feeding a diet inducing weight and fat gain produces different outcomes on iBAT and skeletal muscle UCP mRNA expression, revealing a tissue-dependent response for the three UCPs. Results suggest that the regulation of UCP expression in both tissues under these specific dietary conditions may be related to leptin circulating levels

Evidences on three relevant obesogenes: MC4R, FTO and PPARγ. Approaches for personalized nutrition.

Obesity is a complex disease that results from the interaction between lifestyle (dietary patterns and sedentary habits) and genetic factors. The recognition of a genetic basis for human obesity have driven to identify putative causal genes to understand the pathways that control body mass and fat deposition in humans as well as to provide personalized treatments and prevention strategies to fight against obesity. More than 120 candidate genes have been associated with obesity-related traits. GWAS (genome-wide association study) have so far identified over 20 novel loci convincingly associated with adiposity. This review is specifically focused on the study of the effects of MC4R, PPARγ and FTO gene variants and their interactions with dietary intake, physical activity or drug administration on body weight control. The advances in this field are expected to open new ways in genome-customized diets for obesity prevention and therapy following personalized approaches.

Interaction between genes and lifestyle factors on obesity.

Obesity originates from a failure of the body-weight control systems, which may be affected by changing environmental influences. Basically, the obesity risk depends on two important mutually-interacting factors: (1) genetic variants (single-nucleotide polymorphisms, haplotypes); (2) exposure to environmental risks (diet, physical activity etc.). Common single-nucleotide polymorphisms at candidate genes for obesity may act as effect modifiers for environmental factors. More than 127 candidate genes for obesity have been reported and there is evidence to support the role of twenty-two genes in at least five different populations. Gene-environment interactions imply that the synergy between genotype and environment deviates from either the additive or multiplicative effect (the underlying model needs to be specified to appraise the nature of the interaction). Unravelling the details of these interactions is a complex task. Emphasis should be placed on the accuracy of the assessment methods for both genotype and lifestyle factors. Appropriate study design (sample size) is crucial in avoiding false positives and ensuring that studies have enough power to detect significant interactions, the ideal design being a nested case-control study within a cohort. A growing number of studies are examining the influence of gene-environmental interactions on obesity in either epidemiological observational or intervention studies. Positive evidence has been obtained for genes involved in adiposity, lipid metabolism or energy regulation such as PPARgamma2 (Pro12Ala), beta-adrenoceptor 2 (Gln27Glu) or uncoupling proteins 1, 2 and 3. Variants on other genes relating to appetite regulation such as melanocortin and leptin receptors have also been investigated. Examples of some recently-identified interactions are discussed

Up-regulation of a thermogenesis-related gene (UCP1) and down-regulation of PPARgamma and aP2 genes in adipose tissue: possible features of the antiobesity effects of a beta3-adrenergic agonist.

A number of experiments have demonstrated the antiobesity effects of beta(3)-adrenergic receptor stimulation by promoting thermogenesis and/or lipolysis. While many studies have been performed in order to develop beta(3)-adrenergic agonists as a novel strategy in the management of obesity, more information is needed about the mechanisms involved in thermogenesis and the actions of these drugs on adipocyte differentiation. To address this, the possible thermogenic and antiadipogenic properties of Tertatolol, a beta(3)-adrenergic agonist, in a diet-induced obesity model has been tested. Animals fed on a high-fat diet gained more weight and fat mass as compared with control and high-fat fed animals treated with Tertatolol. A RT-PCR was carried out in white adipose tissue specific genes involved in thermogenesis such as uncoupling proteins (UCPs) and adipogenesis such as peroxisome proliferator-activated receptor (PPARgamma2), retinoid receptors (RXRalpha/RARalpha), and fatty acid binding protein (aP2). Levels of UCP1 mRNA were augmented in the Tertatolol-treated group as compared to non-treated high-fat fed animals, while the beta(3)-adrenergic agonist treatment significantly decreased the expression levels of aP2 and transcription factors such as PPARgamma2 and the ratio RXRalpha/RARalpha as compared to obese rats. Altogether these data suggest that the antiobesity effects of beta(3)-adrenergic agonists are not limited to the promotion of thermogenesis and/or lipolysis and support the implication that these beta(3)-adrenergic agonists also affect fat deposition by impairing adipogenesis in white adipose tissue (WAT)

Changes in objectively measured sleep after a multidisciplinary lifestyle intervention in children with abdominal obesity: A randomized trial

Background/objective: childhood obesity and sleep disorders have a well-established cross-sectional association, but lifestyle interventions’ effects on sleep quality remain under-researched. This study aimed to evaluate the sleep quality of 122 participants (7–16 years) with abdominal obesity after a 2-year necessary lifestyle intervention. Patients/methods: participants were assigned to either the intervention group (moderate hypocaloric Mediterranean Diet) or the usual care group (standard recommendations on a healthy diet). Sleep was objectively assessed using triaxial accelerometry, and sleep parameters analyzed included latency, efficiency, wake after sleep onset, total time in bed, total sleep time, number of awakenings, and awakening duration. Results and conclusions: the results showed that the intervention group significantly improved sleep latency at 12 and 24 months and improved sleep efficiency at 2 and 12 months, compared to the usual care group. Wake after sleep onset and the number of awakenings were significantly reduced at 24 months in the intervention group. Wake after sleep onset and leptin levels were positively associated in all participants. Total time in bed was inversely associated with triglycerides and metabolic score, and total sleep time was inversely associated with leptin, triglycerides, and metabolic score after the 2-month intervention. Triglyceride levels were inversely associated with total time in bed and total sleep time at one year, while the metabolic score was directly associated with wake after sleep onset and the number of awakenings and inversely associated with efficiency. In conclusion, the multidisciplinary intervention in children and adolescents with abdominal obesity reduced anthropometric parameters and improved sleep habits